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WHO NEEDS A WHOLE HEART OR LIVER WHEN:
You can re-create its essential function on a chip // You can use that chip to test drugs // You might someday use the chip to alleviate transplants?

Model Organs in Miniature

By Adam Bluestein // Illustrations by Adam Hayes // Summer 2013
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organs on chips

Adam Hayes

Druing the late 1990s, Linda Griffith was working in the laboratory of Joseph Vacanti, a pioneer in the field of tissue engineering, when she had a revelation. Vacanti, Griffith and their colleagues at Massachusetts General Hospital were working to build a transplantable liver. “The challenges were daunting,” says Griffith, now a professor of biological and mechanical engineering at MIT.

Modern tissue engineering—defined by Vacanti and MIT professor Robert Langer in a 1993 paper in Science—applies concepts and techniques from engineering and life sciences to the problem of cultivating human tissue and whole organs to repair or replace damaged parts of the body. Typically, this involves creating a “scaffold” of natural or synthetic materials, seeding it with human stem cells that can differentiate themselves into particular tissue types, and providing the cells with nutrients and a physical environment that encourages them to take on the three-dimensional structures and functions of a particular body part.

The field has had notable successes—there are people walking around today with lab-grown skin, cartilage, bladders and tracheas—but the goal of building a liver, heart or another large, complex organ remains elusive. Sheer mass is a major issue—it’s very difficult to nourish a 3-D population of cells in the lab on the scale of a liver. And even if you succeed in growing such an organ, transferring it from sterile, controlled conditions into the bloody, chaotic environment of a human being presents its own array of problems.

As Griffith struggled with the technical limitations of her work, she thought more and more about the clinical issues her research was addressing—and her engineer’s mind characteristically flipped the problem. Instead of building a replacement liver, she thought, why not use the same underlying techniques for growing cells in three dimensions to create a better model of how a liver behaves? “As a patient, I’d rather have a cure for my disease, or know how to prevent it, than have an organ transplant,” says Griffith. “It’s very exciting to think about growing a liver or a heart. But I realized that, practically, I could have a lot more impact creating organ models.”

Today, Griffith is a leader in a burgeoning subfield of tissue engineering that does just that: creates microversions of living human organs. These “organs on a chip”—so called for their resemblance to silicon computer microchips—look nothing like the body parts they’re meant to replicate. Generally no bigger than a computer thumb drive and made of clear plastic, the devices contain tiny chambers embedded with populations of living cells and connected by microfluidic channels that control the flow of nutrients and oxygen through the system, mimicking the essential structures and functions of organs such as the lung or liver. Such abilities are proving remarkably useful, with the potential to do everything from reducing dependence on animal models and speeding drug development to demonstrating disease processes—and even, in a neat twist, helping researchers engineer entire implantable organs.

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From Organs to Whole Humans

Tying together multiple organs on a chip could multiply the research benefits of looking at an individual heart or liver. But engineering tiny systems is a huge challenge.

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hed-dossier

1. “Tissue Models: A Living System on a Chip,” Monya Baker, Nature, March 2011. This accessible review article provides a comprehensive overview of the history of organs on a chip and describes major directions in research. 


2. “Engineering Challenges for Instrumenting and Controlling Integrated Organ-on-Chip Systems,” by John Wikswo et al., IEEE Transactions on Biomedical Engineering, March 2013. This technical article details multiple challenges involved in linking multiple organs on chips to create systems that realistically model human physiology.

3. “A Human Disease Model of Drug Toxicity–Induced Pulmonary Edema in a Lung-on-a-Chip Microdevice,” Dongeun Huh et al., Science Translational Medicine, November 2012. A description of how researchers engineered a “sick” lung-on-a-chip that mimics the fluid swelling experienced by some patients taking the anticancer drug interleukin-2. Findings from this model led to the identification of potential drug therapies.

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